Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA), the most common joint disorder worldwide, is characterized by progressive degeneration of articular and periarticular structures, leading to physical and emotional impairments that greatly affect the quality of life of patients. Unfortunately, no therapy has been able to halt the progression of the disease. Owing to the complexity of OA, most animal models are only able to mimic a specific stage or feature of the human disorder. In this work, we demonstrate the intraarticular injection of kaolin or carrageenan leads to the progressive degeneration of the rat's knee joint, accompanied by mechanical hyperalgesia and allodynia, gait impairments (reduced contact area of the affected limb), and radiological and histopathological findings concomitant with the development of human grade 4 OA. In addition, animals also display emotional impairments 4 weeks after induction, namely, anxious and depressive-like behaviour, important and common comorbidities of human OA patients. Overall, prolonging kaolin or carrageenan-induced monoarthritis mimics several important physical and psychological features of human OA in both male and female rodents and could be further applied in long-term studies of OA-associated chronic pain.

Clinical Evolution of Tardive Cervical Dystonia from Antecollis to Retrocollis.

Tardive dystonia occurs after exposure, over months to years, to antipsychotics and other drugs that block dopaminergic receptors. Anterocollis is a rare form of cervical dystonia which is usually disabling for the patient. Here, we present the case of a 61-year-old woman with Alzheimer's dementia diagnosed eight years ago who was previously medicated with antipsychotics. Two years before admission, she was medicated with olanzapine. She presented to the emergency room with a sustained flexion posture of the neck that was difficult to feed. She had a marked and fixed anterocollis and severe akathisia. After the administration of propofol to perform computerized tomography, the abnormal posture disappeared. Subsequently, she was started on biperiden without improvement. One week later, olanzapine was suspended, and she was progressively started on propranolol, trihexyphenidyl, and tetrabenazine. Cervical posture improved, but two weeks later, she presented with a left laterocollis, which allowed feeding, and improvement of akathisia. We present a case of tardive dystonia supported by the beginning of dystonia five months after olanzapine administration and improvement after its suspension. The coexistence of degenerative pathology is a risk factor for dystonia, which often persists despite the suspension of the causative agent. Therefore, non-pharmacological treatment and approach with antipsychotics with a better profile of extrapyramidal effects should be preferred in patients with dementia.

Reversible Bilateral Basal Ganglia Lesions Due to Multifactorial Toxic-Metabolic Disorders.

Bilateral basal ganglia lesions can include a wide variety of etiologies, including metabolic, toxic, degenerative, vascular, inflammatory, infectious, and neoplastic etiology. We present a case of a 78-year-old man who was hospitalized with acute behavioral changes and psychomotor slowing. His medical history included diabetes mellitus, arterial hypertension, and prostate adenocarcinoma. In his spare time, he was a pigeon fancier and regularly burned waste (including diapers) outside his home. In the initial evaluation, he was hypertensive, drowsy, disoriented in time and space, dysarthric, and with global bradykinesia. From the research carried out, we stand out the following: brain magnetic resonance imaging showing bilateral hyperintensity of the basal ganglia on T2/fluid-attenuated inversion recovery, with foci of hypersignal on T1 without diffusion restriction or contrast enhancement; CSF presenting 15 cells/uL, without other alterations; analytical results presenting hypernatremia (171 mEq/L), creatinine at 3.5 mg/dL, hyperglycemia (always <300 mg/dL), and slightly elevated C-reactive protein and anticardiolipin antibodies in addition to thrombocytopenia (107,000). After correcting the metabolic disturbances and evading the identified toxic substances, magnetic resonance imaging showed regression of the lesions, and the patient returned to a normal state. The functions of the basal ganglia are complex, requiring increased use of glucose and oxygen, therefore presenting a high metabolic activity, which makes them vulnerable to various metabolic changes. We report a rare case affected by symmetrical lesions in the basal ganglia and presenting an acute onset of altered mental status with behavioral alterations, related to hyperglycemia, acute kidney injury, hypertension, and exposure to toxic substances (smoke from bonfires and/or toxic chemical components). Complete clinical recovery, remaining negative investigation, and regression of the lesions support our diagnosis.

COVID-19-Associated Encephalitis: Two Case Reports.

The infection with SARS-CoV-2 is primarily associated with respiratory symptoms. Since its appearance, several neurological symptoms have been reported, most commonly headache and anosmia, as well as less frequent complications such as COVID-19-associated encephalitis and meningitis. In this case report, we describe two patients, who were 49- and 50-year-old infected with SARS-CoV-2, who presented to the emergency department with altered mental status and behavioral changes. A diagnosis of acute meningoencephalitis associated with COVID-19 was considered, and both patients had a good response to corticosteroid treatment.

Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

A New Phenotype of Ataxia With Oculomotor Apraxia Type 4.

Ataxia with oculomotor apraxia is a rare neurodegenerative subgroup of diseases with manifestations that include cerebellar ataxia, oculomotor apraxia, extrapyramidal features, and sensorimotor neuropathy. In 2015, ataxia with oculomotor apraxia type 4 was described in 11 Portuguese individuals. The mean age of onset was 4.3 years, with severe extrapyramidal manifestations, neuropathy, rapid progression, and ataxia, being wheelchair-bound during adolescence. The disease is caused by homozygous or compound heterozygous mutations in the PNKP gene. In this case report, we describe two sisters, who were 52- and 58-years-old, with cerebellar dysarthria, oculomotor apraxia, dystonia, and gait ataxia. Two new mutations in the PNKP gene were detected in both sisters, confirming the diagnosis of ataxia with oculomotor apraxia. They were remarkable because they were able to walk unaided during adulthood and had epilepsy. With these clinical cases, we attempt to raise awareness of the possibility of different phenotypes of this rare disease, expanding the spectrum of manifestations of ataxia with oculomotor apraxia type 4.